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2015 ; 12
(ä): 17
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Comprehensive circular RNA profiling reveals that circular RNA100783 is involved
in chronic CD28-associated CD8(+)T cell ageing
#MMPMID26451160
Wang YH
; Yu XH
; Luo SS
; Han H
Immun Ageing
2015[]; 12
(ä): 17
PMID26451160
show ga
BACKGROUND: Ageing brings about the gradual deterioration of the immune system,
also known as immunosenescence. The role of non-coding circular RNA in
immunosenescence is under studied. Using circular RNA microarray data, we
assembled Comparison groups (C1, C2, C3 and C4) that allowed us to compare the
circular RNA expression profiles between CD28(+)CD8(+) T cells and CD28(-)CD8(+)
T cells isolated from healthy elderly or adult control subjects. Using a
step-wise biomathematical strategy, the differentially-expressed circRNAs were
identified in C1 (CD28(+)CD8(+) vs CD28(-)CD8(+)T cells in the elderly) and C4
(CD28(-)CD8(+)T cells in the elderly vs in the adult), and the commonly-expressed
circRNA species from these profiles were optimized as immunosenescence
biomarkers. RESULTS: Four overlapping upregulated circular RNAs (100550, 100783,
101328 and 102592) expressed in cross-comparison between C1 and C4 were validated
using quantitative polymerase chain reaction. Of these, only circular RNA100783
exhibited significant validation. None of the down-regulated circular RNAs were
expressed in the C1 and the C4 cross-comparisons. Therefore, we further predicted
circular RNA100783-targeted miRNA-gene interactions using online DAVID
annotation. The analysis revealed that a circular RNA100783-targeted miRNA-mRNA
network may be involved in alternative splicing, the production of splice
variants, and in the regulation of phosphoprotein expression. Considering the
hypothesis of splicing-related biogenesis of circRNAs, we propose that circular
RNA100783 may play a role in phosphoprotein-associated functions
duringCD28-related CD8(+) T cell ageing. CONCLUSIONS: This study is the first to
employ circular RNA profiling to investigate circular RNA-micro RNA interactions
in ageing human CD8(+)T cell populations and the accompanying loss of CD28
expression. The overlapping expression of circular RNA100783 may represent a
novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing
and global immunosenescence.